Earlier-Life Predictors of Midlife Risk Factors for Alzheimer's Disease: A 35-Year Follow-up

阿尔茨海默病中年危险因素的早期预测因素：35 年随访

• 批准号: 10460376
• 负责人: GEORGE W. REBOK
• 金额: $ 111.47万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10460376
• 关键词: Academic achievement; Address; Adult; Affect; African American; Age; Aging; Alcohols; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Attention Concentration; Baltimore; Behavior; Biological; Biological Markers; Blood; C-reactive protein; CDKN2A gene; Child; Childhood; Chronic stress; Cognition; Cognitive; Communities; Crime; Cyclin-Dependent Kinase Inhibitor; Data; Diabetes Mellitus; Diagnosis; Disease; Drug usage; Elderly; Epigenetic Process; Exposure to; Future; Genetic; Genetic Materials; Health; Home; Hyperlipidemia; Hypertension; Impaired cognition; Imprisonment; Individual; Inflammation; Inflammatory; Interleukin-6; Intervention; Intervention Studies; Interview; Length; Life; Link; Measures; Mental disorders; Methylation; Modification; Not Hispanic or Latino; Obesity; Occupational; Outcome; Outcome Study; Participant; Pathway interactions; Physiological; Police; Poverty; Prevention; Prevention Research; Prevention trial; Psychopathology; Public Health; Race; Risk; Risk Factors; Role; Sampling; Sleep; Sleep disturbances; Smoking; Social support; Stress; Subgroup; Symptoms; TNF gene; Time; Trauma; Violence; Wrist; achievement test; actigraphy; cognitive performance; cohort; conduct problem; dementia risk; disorder risk; early life stress; first grade; follow-up; health disparity; high risk; indexing; inflammatory marker; middle age; modifiable risk; poor sleep; prevent; preventive intervention; prospective; protective factors; racial discrimination; racial disparity; risk variant; second grade; sex; stressor; substance use; telomere; universal prevention; young adult

Alzheimer’s disease (AD) is a public health crisis in the US and a growing health disparity, with African Americans (AAs) two to three times more likely to be diagnosed with the disease than non-Hispanic whites. Efforts to identify modifiable earlier-life risk and protective factors for known midlife risk factors for poor cognitive outcomes in later life are needed to protect the health of middle-aged and older AAs. We propose to prospectively examine trajectories of individual- and community-level stress exposures from childhood to early midlife as predictors of known midlife risk factors for subsequent Alzheimer’s disease and related dementias (ADRD) in two primarily (~66%) AA cohorts that are now ages 40-44 and have been followed repeatedly from age 6 to age 32 (2009-2011) by the Johns Hopkins Prevention Intervention Research Center (PIRC). Relevant individual- and community-level stress exposures that occur from early life to middle adulthood include: 1) adverse life circumstances and trauma (i.e., extreme poverty, residential instability, crime, police and community violence, incarceration, racial discrimination); 2) mental disorders and their symptoms; and 3) poor sleep (e.g., abnormal duration, fragmentation). Additionally, these stress exposures have been linked to other risk factors for AD including obesity, hypertension, and diabetes by which AAs are disproportionately affected. We aim to determine the extent to which ~35-year trajectories of stress exposures are associated with risk for later-life ADRD measured in early midlife using a dementia risk index, and with early-midlife measures of physiological aging (telomere length, p16, methylation age), epigenetic modification, inflammation, and cognitive performance. We will also examine if these associations are moderated by sex, race, and AD risk genes, and explore how the timing of exposures in the lifecourse, and other potential moderators (i.e., childhood academic achievement, educational/occupational attainment, alcohol/drug use, smoking, conduct problems, social support, perceived control), affect these associations. Further, we will explore the effects of two early-life (ages 6-8) PIRC interventions on our early midlife study outcomes. To accomplish this, we will repeat blood and buccal sampling for genetic and epigenetic material and complete two in-home interviews, including a cognitive battery and actigraphic sleep assessments, with 1,150 participants. This study is a rare opportunity to clarify links of earlier-life stress exposures with midlife dementia risk, identify vulnerable subgroups for targeted ADRD prevention, elucidate the role of social inequities in determining racial disparities in AD dementia, and establish a midlife cognitive baseline for future follow-up of these unusually well-characterized longitudinal, primarily AA cohorts.

阿尔茨海默氏病（AD）是美国的公共卫生危机，而且健康差异不断增加 美国人（AAS）被诊断出患有该疾病的可能性是非西班牙裔白人的两倍。 努力确定已知的中年风险因素的可修改的早期风险和保护因素 需要以后的生活中的认知结果来保护中年和年长的AA的健康。我们建议 前瞻性地检查从童年到个人和社区水平的压力暴露的轨迹 中年早年作为随后的阿尔茨海默氏病及相关的已知中年危险因素的预测因素 痴呆症（ADRD）在两个年龄为40-44岁的主要（约66％）的AA同类中，已遵循 约翰·霍普金斯预防干预研究从6岁到6岁至32岁（2009-2011） 中心（PIRC）。从早期到 成年中期包括：1）不利的生活环境和创伤（即极端贫困，居民 不稳定，犯罪，警察和社区暴力，事件，种族歧视）； 2）精神障碍 及其症状； 3）睡眠不佳（例如，持续时间异常，碎片化）。另外，这些压力 暴露与其他广告的风险因素有关，包括肥胖，高血压和糖尿病 AA受到不成比例的影响。我们旨在确定〜35年轨迹的程度 压力暴露与使用痴呆症在中年早年测量的后期ADRD风险有关 风险指数，并采用早期生活的身体衰老（端粒长度，p16，甲基化年龄）， 表观遗传修饰，炎症和认知性能。我们还将检查这些是否 性，种族和广告风险基因的协会调节，并探索暴露时间如何 生命力和其他潜在的主持人（即儿童学术成就， 教育/职业尝试，饮酒/吸毒，吸烟，引起问题，社会支持， 感知控制），影响这些关联。此外，我们将探索两个早期生活的影响（6-8岁） PIRC干预我们早期的中年研究结果。为此，我们将重复血液， 遗传和表观遗传材料的颊抽样，并完成两次家庭访谈，包括A 认知电池和行动式睡眠评估，有1,150名参与者。这项研究是罕见的 有机会澄清早期生活压力与中年痴呆症风险的联系，确定弱势群体 针对有针对性的预防ADRD的亚组，阐明了社会不平等在确定种族中的作用 AD痴呆症的差异，并建立了中年认知基线，以使这些不寻常的随访 特征纵向的纵向，主要AA队列。